Promotion by the alpha-adrenoceptor agonist phenylephrine, but not by the beta-adrenoceptor agonist isoproterenol, of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
The effects of prolonged administration of the alpha-adrenoceptor agonist phenylephrine and the beta-adrenoceptor agonist isoproterenol on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and on the labeling index of gastric mucosa were compared in Wistar rats. Rats received subcutaneous injections of 3 or 6 mg/kg body weight of phenylephrine or 0.1 or 0.2 mg/kg body weight of isoproterenol every other day after 25 weeks of oral treatment with the carcinogen. Long-term administration of phenylephrine at a high dose, but not at a low dose, significantly increased the incidence of gastric cancers and the labeling index of antral epithelial cells at the end of the experiment in week 52. However, administration of isoproterenol at either dosage had no significant effect on the incidence of gastric cancers and the labeling index of antral epithelial cells. These findings indicate that increased activity of the sympathetic nervous system enhances gastric carcinogenesis through alpha-adrenoceptors.
Iishi
H
H
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Tatsuta
M
M
Baba
M
M
Sakai
N
N
Yano
H
H
Uehara
H
H
Nakaizumi
A
A
Iseki
K
K
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D008769:Methylnitronitrosoguanidine; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D013274:Stomach Neoplasms / Q000139:chemically induced*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha; D008769:Methylnitronitrosoguanidine; D010656:Phenylephrine; D007545:Isoproterenol